Therapeutic uses of polymers and oligomers comprising gamma-hydroxybutyrate

Abstract

Oligomers and polymer compositions are provided which comprise GHB and produce GHB after administration in vivo. Devices for the storage and delivery of these polymers and oligomers are also provided. These oligomers and polymer compositions are useful in a variety of applications. The compositions can be used therapeutically, for example, in the treatment of patients with narcolepsy, chronic schizophrenia, catatonic schizophrenia, atypical psychoses, chronic brain syndrome, neurosis, alcoholism, drug addiction and withdrawal, Parkinson's disease and other neuropharmacological illnesses, hypertension, ischemia, circulatory collapse, radiation exposure, cancer, and myocardial infarction. Other uses for the compositions include anesthesia induction, sedation, growth hormone production, heightened sexual desire, anorectic effects, euphoria, smooth muscle relaxation, muscle mass production, and sleep, including rapid eye movement sleep. In a still further embodiment, the oligomers and polymers may be used to produce absence seizures.

We claim:  
     
       1. A composition for modulating endogenous levels of gamma-hydroxybutyrate in a patient comprising a dosage formulations in a form acceptable for enteral or parenteral administration to a patient in need thereof, the formulation comprising 
       a polymer or oligomer which comprises a gamma-hydroxybutyrate in an ester or polyester form,  
       wherein the polymer or oligomer, When administered to the patient, is metabolized to release an effective amount of the gamma-hydroxybutyrate in vivo.  
     
     
       2. The composition of  claim 1  wherein the polymer or oligomer is poly-gamma-hydroxybutyrate. 
     
     
       3. The composition of  claim 1  wherein the polymer or oligomer is a copolymer comprising gamma-hydroxybutyrate. 
     
     
       4. The composition of  claim 3  wherein the copolymer further comprises a second hydroxyalkanoate monomer. 
     
     
       5. The composition of  claim 4  wherein the copolymer is poly-β-hydroxybutyrate-co-β-hydroxybutyrate. 
     
     
       6. The composition of  claim 1  wherein the oligomer is a cyclic oligomer. 
     
     
       7. The composition of  claim 1  further comprising gamma-hydroxybutyrate monomer. 
     
     
       8. The composition of  claim 1  in a formulation suitable for intravenous administration. 
     
     
       9. The composition of  claim 1  in a formulation suitable for oral administration. 
     
     
       10. The composition of  claim 1  in a formulation suitable for implantation. 
     
     
       11. The composition of  claim 1  wherein the polymers and oligomers are derived from biomass. 
     
     
       12. The composition of  claim 1  in a dosage formulation for the treatment of patients having a disease selected from the group consisting of narcolepsy, chronic schizophrenia, catatonic schizophrenia, atypical psychoses, chronic brain syndrome, neurosis, alcoholism, drug addiction and withdrawal, Parkinson's disease and other neuropharmacological illnesses, hypertension, ischemia, circulatory collapse, radiation exposure, cancer, myocardial infarction, fibromyalgia, and chronic fatigue syndrome, reperfusion, and inflammation. 
     
     
       13. The composition of  claim 1  in a dosage formulation to induce a condition selected from the group consisting of anesthesia, sedation, growth hormone production, anorectic effects, euphoria, smooth muscle relaxation, muscle mass production, heightened sexual desire, sleep, and prolactin release. 
     
     
       14. The composition of  claim 1  in a dosage formulation suitable to produce absence seizures. 
     
     
       15. The composition of  claim 1  that can elevate gamma-hydroxybutyrate levels in vivo for more than four hours. 
     
     
       16. A method of modulating gamma-hydroxybutyrate levels in vivo comprising administering to a human or animal a polymer or oligomer composition comprising gamma-hydroxybutyrate in an ester or polyester form wherein the composition is in a form acceptable for enteral or parental administration. 
     
     
       17. The method of  claim 16  wherein the composition produces a gamma-hydroxybutyrate level effective to treat patients with a disorder selected from the group consisting of narcolepsy, chronic schizophrenia, catatonic schizophrenia, atypical psychoses, chronic brain syndrome, neurosis, alcoholism, drug addiction and withdrawal, Parkinson's disease and other neuropharmacological illnesses, hypertension, ischemia, circulatory collapse, radiation exposure, cancer, myocardial infarction, reperfusion, and inflammation. 
     
     
       18. The method of  claim 17  wherein the patient has cancer and the composition provides for the sustained release of gamma-hydroxybutyrate in an anti-angiogenically effective amount. 
     
     
       19. The method of  claim 16  wherein the composition produces a gamma-hydroxybutyrate level effective to induce a condition selected from the group consisting of anesthesia, sedation, growth hormone production, anorectic effects, euphoria, smooth muscle relaxation, muscle mass production, heightened sexual desire, and sleep. 
     
     
       20. The method of  claim 16  wherein the composition is administered orally or by injection or implantation. 
     
     
       21. The method of  claim 16  wherein the composition is administered as a hypnotic. 
     
     
       22. The method of  claim 16  wherein the composition is administered as a neurotransmitter or neuromodulator. 
     
     
       23. The method of  claim 16  wherein the composition is administered to increase gastric emptying or to treat malabsorption disorders. 
     
     
       24. A method for making oligomers comprising gamma-hydroxybutyrate comprising the steps: 
       a) selecting a polymer comprising gamma-hydroxybutyrate, and  
       b) hydrolyzing or transesterifying the polymer to produce oligomers having number average molecular weights above 3,000.  
     
     
       25. A therapeutic composition comprising a gamma-hydroxybutyrate prodrug in an ester or polyester form in a polymer or oligomer that can modulate endogenous levels of gamma-hydroxybutyrate in vivo wherein the composition is in a form acceptable for enteral or parenteral administration. 
     
     
       26. The composition of  claim 25  wherein the gamma-hydroxybutyrate prodrug is an orthoester. 
     
     
       27. The composition of  claim 25  wherein the polymers and oligomers are derived from gamma-butyrolactone. 
     
     
       28. The composition of  claim 25  wherein the polymers or oligomers are used for the slow or sustained release of gamma-hydroxybutyrate. 
     
     
       29. The method of  claim 16  wherein the polymers or oligomers are used to treat cancer or prevent metastasis.